OBJECTIVES: 1) To investigate the structure-activity relationships among the quassinoid related compounds for in vivo antileukemic activity. 2) To determine whether the possession of at least one diosphenol type alkylating function and a carrier ester side chain is a consistent parameter for potent antileukemic activity. 3) To prepare the diosphenol type bi- and poly-functional alkylating quassinoid analogs for possible enhancement of antileukemic activity. 4) To introduce various carrier moieties into the diosphenol bearing quassinoids for possible therapeutic antileukemic agents. METHODS: 1) Bruceins-D and -E as well as quassin and neoquassin will be obtained from the plant extract. 2) New synthetic mono- to poly-alkylating functional derivatives related to bruceins-D and -E as well as quassin and neoquassin with modification of the diosphenol system and variation of the carrier ester side chain will be prepared and their in vivo antileukemic activity (P388) evaluated. 3) The carrier moieties chosen are fatty acids, steroids, steroidal hormones, nitrosoureas, sugars and amino sugar daunosamine. 4) Modern physical methods, such as UV, IR, NMR, C-13, ORD, CD, mass spectrometry, X-ray analysis, as well as elemental analysis and thin layer chromatography will be used to elucidate and confirm the structures and stereochemistry of the compounds prepared. 5) Those compounds which proved to be very active in the in vivo P388 screen will be further tested for their effects on L-1210 leukemia, Lewis lung carcinoma, B-16 melanocarcinoma, Walker 256 carcinosarcoma and Ehrlich ascites carcinoma.